sildenafil-citrate and Retinal-Diseases

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

Topics: Anemia, Sickle Cell; Blood Transfusion; Clinical Trials as Topic; Disease Management; Gastrointestinal Diseases; Humans; Hydroxyurea; Hypertension, Pulmonary; Muscular Diseases; Nervous System Diseases; Pain; Phenotype; Piperazines; Purines; Retinal Diseases; Sildenafil Citrate; Sulfones; Treatment Outcome

Drug-induced retinopathies are rare conditions produced by a large variety of medications. There are several specific patterns of retinal toxicity, which should be recognized and correlated with the clinical state.

Topics: Chloroquine; Humans; Phenothiazines; Piperazines; Purines; Retinal Diseases; Sildenafil Citrate; Sulfones; Tamoxifen; Vasodilator Agents

Retinal vascular tortuosity is associated with retinopathy of differing etiologies, including hypertension, diabetes, and hypoxia. However, detailed understanding of the underlying pathophysiology is lacking. The aim of this study was to map changes in tortuosity associated with hypoxia at high altitude, and to determine the influence of sildenafil and an antioxidant preparation on altitude-induced tortuosity.. We measured the tortuosity of retinal vessels using a semi-automated method in 35 young, healthy subjects exposed to hypobaric hypoxia for 7 days at 5200 m, and compared the measurements to those from the same vessels at sea level. These subjects simultaneously took part in a randomized double-blind placebo-controlled trial of sildenafil and antioxidant. Comparison of tortuosity between these subgroups was performed.. High altitude was associated with the development of retinal tortuosity in individual vessels. A nonsignificant trend suggests this is limited by prophylaxis with sildenafil or antioxidant.. Retinal vessel tortuosity increases rapidly at high altitude. We suggest that retinal vessel tortuosity at altitude may result from increased sheer stress causing elongation of vessel segments and that this might be limited by agents that act to preserve nitric oxide dependent vasodilation.. NCT00664001, NCT00627965.

Topics: Adolescent; Adult; Altitude; Antioxidants; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypoxia; Male; Mountaineering; Photography; Piperazines; Purines; Retinal Diseases; Retinal Vessels; Sildenafil Citrate; Sulfones; Vasodilator Agents; Young Adult

Topics: Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Retinal Diseases; Sildenafil Citrate; Vasodilator Agents

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia-reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty-six rats were divided into a control group (n = 6) and two experimentally induced ischaemia-reperfusion groups (7 and 21 days; n = 15 per group). The induced ischaemia-reperfusion groups were treated with sildenafil for 7 and 21 days (n = 10 per group), and 10 animals were treated with a placebo for the same period (n = 5 per group). Paracentesis of the anterior chamber was performed with a 30-G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet

Topics: Animals; Apoptosis; Drug Evaluation, Preclinical; Eye Proteins; Gene Expression Regulation; Intraocular Pressure; Male; Optic Nerve; Rats, Inbred Lew; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels; Sildenafil Citrate; Vasodilator Agents

Retinal ischemia is a common cause of visual impairment and blindness. Sildenafil, a PDE5 inhibitor which inhibits cGMP degradation and in turn prolongs the effect of nitric oxide, has been shown to be protective in a number of ischemia/reperfusion (I/R) injuries, as well as in neuronal damage. We hypothesized that treatment with sildenafil might be neuroprotective in a model of acute retinal I/R injury.. Anterior chamber cannulation was performed to induce unilateral I/R injury in 38 Lewis rats. Animals received intraperitoneal injections of sildenafil (0.5 and 1 mg/kg once a day, for a period of 7 and 18 days, respectively), or saline. Electroretinography recordings, retinal ganglion cell (RGC) counts following retrograde labeling with fluorogold, histopathology, and immunohistochemistry (IHC) using antibodies against PDE5, NOS2, caspase-3, caspase-9, and Bcl-2 were conducted.. No significant differences in electroretinography, RGC counts, or retinal morphometry were observed between experimental eyes of sildenafil- and saline-treated animals. A tendency toward less necrosis in histopathology, and a slight trend toward lower PDE5, NOS2, and caspase-9 and higher Bcl-2 IHC scores were evident in experimental retinas of sildenafil-treated animals.. Electroretinography, RGC counts, and retinal morphometry failed to show any neuroprotective effect of sildenafil in acute retinal I/R injury in rats. A slight positive effect of sildenafil was qualitatively indicated by histopathology and IHC.

Topics: Animals; Caspase 3; Caspase 9; Cell Count; Disease Models, Animal; Electroretinography; Immunohistochemistry; In Situ Nick-End Labeling; Male; Phosphodiesterase 5 Inhibitors; Rats; Rats, Inbred Lew; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Sildenafil Citrate; Treatment Outcome

The aim of this study was to investigate possible functional and structural ocular changes caused by chronic sildenafil therapy to treat pulmonary arterial hypertension (PAH).. Case-control study included patients with pulmonary arterial hypertension: chronically using sildenafil and without sildenafil treatment. A comprehensive ophthalmologic exam including ectoscopy, extrinsic ocular motility, logMAR visual acuity measurement, contrast sensitivity test, color test, anterior segment biomicroscopy, Schirmer test 1, intraocular pressure, fundus exam under pupil dilation, fundus pictures, time domain and spectral domain optical coherence tomography, ocular Doppler ultrasound were performed. Full-field electroretinography (ERG) was tested for each eye in a subgroup of sildenafil-treated patients.. Twenty patients from each group were tested. Bilateral severe keratitis was found in seven (35 %) patients under sildenafil therapy. Lacrimal film break-up time (BUT) was significantly reduced (p = 0.006 respectively) and Doppler ultrasound showed a reduced resistance index of the central retinal artery in the group of sildenafil users (p = 0.019). No diffuse retinal functional abnormalities were found in ERG in treated patients. Visual acuity, contrast sensitivity and color discrimination were normal in both groups. No abnormalities were found in both time-domain and spectral-domain OCT for retinal parameters.. One-third of the treated PAH group showed severe bilateral keratitis. This finding could be related to connective tissue abnormalities usually present in patients with this condition that might be exacerbated with the sildenafil usage. The resistance index of the central retinal artery was diminished in the chronic users group and it could be associated to the vasodilation caused by the medication in the choroidal vessels. An ophthalmic assessment for these patients is recommended to diagnose and treat possible ocular surface and choroidal blood flow abnormalities caused by sildenafil.

Topics: Adult; Aged; Blood Flow Velocity; Case-Control Studies; Electroretinography; Female; Humans; Hypertension, Pulmonary; Keratitis; Lacrimal Apparatus Diseases; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Retinal Artery; Retinal Diseases; Sildenafil Citrate; Ultrasonography, Doppler, Color; Visual Acuity

The purpose of this study was to investigate the effects of sildenafil on retinal injury following neonatal hypoxia-ischemia (HI) at term-equivalent age in rat pups.. Hypoxia-ischemia was induced in male Long-Evans rat pups at postnatal day 10 (P10) by a left common carotid ligation followed by a 2-hour exposure to 8% oxygen. Sham-operated rats served as the control group. Both groups were administered vehicle or 2, 10, or 50 mg/kg sildenafil, twice daily for 7 consecutive days. Retinal function was assessed by flash electroretinograms (ERGs) at P29, and retinal structure was assessed by retinal histology at P30.. Hypoxia-ischemia caused significant functional (i.e., attenuation of the ERG a-wave and b-wave amplitudes and photopic negative response) and structural (i.e., thinning of the total retina, especially the inner retinal layers) retinal damage in the left eyes (i.e., ipsilateral to the carotid ligation). Treatment with the different doses of sildenafil led to a dose-dependent increase in the amplitudes of the ERG a- and b-waves and of the photopic negative response in HI animals, with higher doses associated with greater effect sizes. Similarly, a dose response was observed in terms of improvements in the retinal layer thicknesses.. Hypoxia-ischemia at term-equivalent age induced functional and structural damage mainly to the inner retina. Treatment with sildenafil provided a dose-dependent recovery of retinal function and structure.

Topics: Administration, Oral; Animals; Animals, Newborn; Disease Models, Animal; Electroretinography; Female; Follow-Up Studies; Hypoxia; Male; Phosphodiesterase 5 Inhibitors; Rats; Rats, Long-Evans; Reperfusion Injury; Retina; Retinal Diseases; Sildenafil Citrate

: To investigate a suspected relationship between central serous chorioretinopathy (CSC) and sildenafil therapy.. : For this retrospective, observational case series, the authors reviewed over 1,500 case reports of sildenafil-associated ocular side effects from the postmarketing surveillance databases of the Food and Drug Administration (FDA), the World Health Organization (WHO), and the National Registry of Drug-Induced Ocular Side Effects. They also performed a Medline literature search for "retinopathy, retinal edema, macular edema" (terms associated with CSC) and "sildenafil." They identified 11 cases of CSC in men taking sildenafil.. : In 8 of 11 cases, patients stopped sildenafil therapy when CSC occurred. In 6 of these 8 cases, patients' vision improved after sildenafil cessation. In 3 cases, effects recurred when patients resumed sildenafil therapy, but stopping therapy was not associated with improvement of CSC in every case. Two patients continued to experience CSC after sildenafil cessation.. : Practitioners who see patients with refractory CSC should consider recommending cessation of sildenafil therapy; however, because of the cyclic nature of CSC, a causal relationship has not yet been established. Additional possible case reports can be sent to the National Registry of Drug-Induced Ocular Side Effects, the FDA, the WHO, or the manufacturer.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Choroid Diseases; Databases, Factual; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Product Surveillance, Postmarketing; Purines; Retinal Diseases; Retrospective Studies; Serum; Sildenafil Citrate; Sulfones